A great deal of information is available on the pathology of human alcoholism, yet the precise mechanisms of ethanol action are very poorly understood. The cytotoxic effects following chronic alcohol exposure may be due to ethanol directly, or the result of exposure to one of the metabolites of alcohol oxidation. In the primary pathway of alcohol metabolism, acetaldehyde is produced from ethanol through the action of the enzyme alcohol dehydrogenase (ADH). The acetaldehyde is then further oxidized to the harmless metabolite acetate through the action of acetaldehyde dehydrogenase. At present, acetaldchyde is believed to be the toxic element responsible for much of the complex pathology associated with alcoholism. We have utilized immunocytochemistry procedures to identify ADH within selected regions of the rat brain that are known to be damaged in Wernicke's encephalopathy of alcoholism (18-20). We hypothesize that the local production of acetaldehyde in these locations is responsible for the subsequent CNS symptomology. We have localized ADH using normal animals that have never been given alcohol. The goal of this proposal is to investigate the effects of both acute and chronic alcohol administration on the distribution of ADH. We plan to examine this enzyme in the brain as well as in other organs known to be included in the pathology of alcoholism, such as the testes, stomach, intestines, kidney, and spleen. Included in this project will be the construction of an "ADH map" of the central nervous system which pinpoints the response of the brain to acute and chronic alcohol exposure.